Antigen Nonspecific Induction of Distinct Regulatory T Cell States in Oncogene-Driven Hyperproliferative Skin
Open Access
- 1 February 2021
- journal article
- Published by The American Association of Immunologists in ImmunoHorizons
- Vol. 5 (2), 102-116
- https://doi.org/10.4049/immunohorizons.2100006
Abstract
Regulatory T cells (Tregs) are recruited to nonlymphoid tissues in chronic disease, including cancer, and the tissue environment is held to shape the Treg phenotype diversity. Using single-cell RNA sequencing, we examined the transcriptomic and TCR profile of Tregs recruited to hyperproliferative HPV16 E7–expressing transgenic and control nontransgenic murine skin grafts. Tregs were more abundant in E7 transgenic skin grafts than control grafts, without evidence of E7 specificity. E7 transgenic grafts attracted both Klrg1+ Tregs and Il1r2+ Tregs, which were phenotypically distinct but shared a core gene signature with previously described tumor-infiltrating Tregs. Pseudotime trajectory analysis of Tregs of defined TCR clonotypes predicted phenotypic plasticity within the skin and between the skin and draining lymph nodes. Thus, oncogene-induced hyperproliferative skin expressing a single defined non–self-antigen can attract and induce non–Ag-specific Tregs that acquire distinct regulatory phenotypes characterized by specific effector gene signatures.Keywords
This publication has 55 references indexed in Scilit:
- Bystander-Activated Memory CD8 T Cells Control Early Pathogen Load in an Innate-like, NKG2D-Dependent MannerCell Reports, 2013
- CD4+ T-cell response against human papillomavirus type 16 E6 protein is associated with a favorable clinical trendCancer Immunology, Immunotherapy, 2011
- The Toll-Like Receptor 2 Pathway Establishes Colonization by a Commensal of the Human MicrobiotaScience, 2011
- IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytesExperimental Dermatology, 2010
- Surgery followed by Persistence of High-Grade Squamous Intraepithelial Lesions Is Associated with the Induction of a Dysfunctional HPV16-Specific T-Cell ResponseClinical Cancer Research, 2008
- CD4+CD25hi regulatory T‐cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasiaInternational Journal of Cancer, 2007
- Association of cervical cancer with the presence of CD4+regulatory T cells specific for human papillomavirus antigensProceedings of the National Academy of Sciences of the United States of America, 2007
- Impaired Antigen Presentation and Effectiveness of Combined Active/Passive Immunotherapy for Epithelial TumorsJNCI Journal of the National Cancer Institute, 2004
- Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by LipopolysaccharideThe Journal of Experimental Medicine, 2003
- Presentation of the HPV16E7 Protein by Skin Grafts Is Insufficient to Allow Graft Rejection in an E7-Primed AnimalVirology, 1997